title: GDF-15 protects from macrophage accumulation in a mousemodel of advanced atherosclerosis.
abstract: BACKGROUND
  The cytokine growth differentiation factor-15 (GDF-15), a member of the TGF beta superfamily, has recently been discovered to play an important role in cardiovascular diseases. It is mostly expressed in macrophages of atherosclerotic lesions, but its impact on advanced atherosclerosis is still unknown. This study was performed to evaluate the effects of GDF-15 in an established mouse model of advanced atherosclerosis.
  
  
  METHODS
  Thirty-eight LDL receptor deficient mice received a lethal body radiation. Half of the group was transplanted with bone marrow of GDF-15 deficient mice. Nineteen mice were transplanted with bone marrow from wild-type controls. After 24 weeks on an atherogenic diet, animals were euthanized and sections of the aortic sinus were prepared. Lesion size and lesion composition, as well as macrophage content,were evaluated.
  
  
  RESULTS
  While demonstrating no difference in lesion size, LDL-receptor knockout mice transplanted with bone marrow from GDF-15 deficient mice showed enhanced macrophage accumulation and features of atherosclerotic plaque destabilization, such as thinning of fibrous caps. Immunostaining against intercellular adhesion molecule-1 further revealed an increased expression in mice receiving GDF-15-deficient bone marrow.
  
  
  CONCLUSIONS
  This is the first study that demonstrates a protective role of GDF-15 in advanced atherosclerosis and macrophage accumulation, possibly due to the reduced expression of adhesion molecules.
authors.affiliation: Department of Internal Medicine, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Preusch
authors.forename: Matthias
authors.initials: M
authors.lastname: Baeuerle
authors.forename: Claudia
authors.initials: C
authors.lastname: Albrecht
authors.forename: Erwin
authors.initials: E
authors.lastname: Blessing
authors.forename: Marc
authors.initials: M
authors.lastname: Bischof
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Florian
authors.initials: F
authors.lastname: Bea
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion / Q000235:genetics / Q000528:radiation effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004195:Disease Models, Animal; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007928:Lethal Dose 50; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014916:Whole-Body Irradiation
chemical_list: D015815:Cell Adhesion Molecules; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D011973:Receptors, LDL